Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity

• Published in: British journal of haematology Vol. 97; no. 3; pp. 641 - 648
• Main Authors: Diamond, T., Levy, S., Day, P., Barbagallo, S., Manoharan, A., Kwan, Y. K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.1997; Blackwell
• Subjects: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers - blood; Bone Density; Bone Resorption; Calcium - blood; Female; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Male; Medical sciences; Middle Aged; multiple myeloma; Multiple Myeloma - complications; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Osteocalcin - blood; osteoporosis; Osteoporosis - drug therapy; Osteoporosis - etiology; Osteoporosis - metabolism; Peptide Fragments - blood; Peptides - blood; Phosphates - blood; Vitamin D - blood; Human; Corticosteroid; Immunopathology; Steroid hormone; Pathogenesis; Diseases of the osteoarticular system; Evolutivity; Malignant hemopathy; Bone disease; Histology; Myeloma; Glucocorticoid; Osteoporosis; Chemotherapy; Treatment; Immunoglobulinopathy; Lymphoproliferative syndrome; Densitometry; Morphometry; High dose
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1997.1042920.x

It is unknown whether bone changes which can occur in multiple myeloma (MM) are due to cytokine‐induced osteoclastic bone resorption from a clone of abnormal plasma cells or high‐dose glucocorticoid therapy. We studied 25 MM patients treated for 1–12 years with combination chemotherapy, subdivided into two groups. Group 1 consisted of 12 patients with stage I and II myeloma and group 2 consisted of 13 patients with stage III MM. Their serum biochemistry, tetracycline‐labelled bone histomorphometry and bone densitometry were compared to age‐ and sex‐matched controls. Patients with MM demonstrated increased indices of bone resorption (P<0.001 versus controls) and, to a lesser extent, increased indices of bone formation (P<0.01 versus controls). No patient had evidence of a mineralization defect. Lumbar spine, femoral neck and total body bone mineral density measurements (BMD) were significantly lower in group 2 compared with group 1 (P<0.05). Following 12 months of therapy, lumbar spine BMD decreased by 6.6% (95% CI, 2.7% to −9.3%) and femoral neck BMD decreased by 9.5% (95% CI, −3.2% to −15.9%). In a stepwise regression analysis, cumulative prednisolone dosage (B Coef.=−0.39; P=0.03) and plasma cell infiltrate (B Coef.=−0.08; P=0.05) were the most important predictors of lumbar spine bone loss, whereas serum paraprotein (B Coef.=−0.35; P=0.02) and plasma cell infiltrate (B Coef.=−0.20; P=0.04) were the most important predictors of femoral neck bone loss. We conclude that MM is characterized by high bone turnover with osteoblast–osteoclast uncoupling. Both disease activity and high‐dose glucocorticoid therapy may be responsible for the ongoing bone loss seen with MM.